Jackson–Weiss syndrome (JWS) is a

genetic disorder A genetic disorder is a health problem caused by one or more abnormalities in the genome. It can be caused by a mutation in a single gene (monogenic) or multiple genes (polygenic) or by a chromosome abnormality. Although polygenic disorders ...

characterized by foot abnormalities and the premature fusion of certain bones of the skull (

craniosynostosis Craniosynostosis is a condition in which one or more of the fibrous sutures in a young infant's skull prematurely fuses by turning into bone (ossification), thereby changing the growth pattern of the skull. Because the skull cannot expand perpe ...

), which prevents further growth of the skull and affects the shape of the head and face. This genetic disorder can also sometimes cause

intellectual disability Intellectual disability (ID), also known as general learning disability (in the United Kingdom), and formerly mental retardation (in the United States), Rosa's Law, Pub. L. 111-256124 Stat. 2643(2010).Archive is a generalized neurodevelopmental ...

and crossed eyes. It was characterized in 1976.subscription required

Signs and symptoms

Many of the characteristic facial features (among other) of Jackson–Weiss syndrome result from the premature fusion of the skull bones. The following are some of the more common, such as: * Preaxial foot

polydactyl Polydactyly is a birth defect that results in supernumerary body part, extra fingers or toes. The hands are more commonly involved than the feet. Extra fingers may be painful, affect self-esteem, or result in clumsiness. It is associated with ...

* Tarsal synostosis *

Frontal bossing Skull bossing is a descriptive term in medical physical examination indicating a protuberance of the skull, most often in the frontal bones of the forehead ("frontal bossing"). Although prominence of the skull bones may be normal, skull bossing may ...

Proptosis Exophthalmos (also called exophthalmus, exophthalmia, proptosis, or exorbitism) is a bulging of the eye anteriorly out of the orbit. Exophthalmos can be either bilateral (as is often seen in Graves' disease) or unilateral (as is often seen in ...

Craniosynostosis Craniosynostosis is a condition in which one or more of the fibrous sutures in a young infant's skull prematurely fuses by turning into bone (ossification), thereby changing the growth pattern of the skull. Because the skull cannot expand perpe ...

* Midfacial hypoplasia * Acrocephaly * Flat

occiput The occipital bone () is a cranial dermal bone and the main bone of the occiput (back and lower part of the skull). It is trapezoidal in shape and curved on itself like a shallow dish. The occipital bone lies over the occipital lobes of the ...

Ocular hypertelorism Hypertelorism is an abnormally increased distance between two organs or bodily parts, usually referring to an increased distance between the orbits (eyes), or orbital hypertelorism. In this condition, the distance between the inner eye corners, a ...

* Downslanted palpebral fissures * Ptosis *

Strabismus Strabismus is an eye disorder in which the eyes do not properly align with each other when looking at an object. The eye that is pointed at an object can alternate. The condition may be present occasionally or constantly. If present during a ...

* Flat nasal bridge * Maxillary hypoplasia *

Cleft palate A cleft lip contains an opening in the upper lip that may extend into the nose. The opening may be on one side, both sides, or in the middle. A cleft palate occurs when the palate (the roof of the mouth) contains an opening into the nose. The ...

* Malformed ears

Genetics

Mutations in the

FGFR2 Fibroblast growth factor receptor 2 (FGFR-2) also known as CD332 (cluster of differentiation 332) is a protein that in humans is encoded by the ''FGFR2'' gene residing on chromosome 10. FGFR2 is a receptor for fibroblast growth factor. FGFR-2 is ...

gene In biology, the word gene has two meanings. The Mendelian gene is a basic unit of heredity. The molecular gene is a sequence of nucleotides in DNA that is transcribed to produce a functional RNA. There are two types of molecular genes: protei ...

cause Jackson–Weiss syndrome. The FGFR2 gene produces a

protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residue (biochemistry), residues. Proteins perform a vast array of functions within organisms, including Enzyme catalysis, catalysing metab ...

called

fibroblast growth factor receptor 2 Fibroblast growth factor receptor 2 (FGFR-2) also known as CD332 (cluster of differentiation 332) is a protein that in humans is encoded by the ''FGFR2'' gene residing on chromosome 10. FGFR2 is a receptor for fibroblast growth factor. FGFR-2 is ...

, which occurs in chromosome number 10. Among its multiple functions, this protein signals immature cells to become bone cells in a developing

embryo An embryo ( ) is the initial stage of development for a multicellular organism. In organisms that reproduce sexually, embryonic development is the part of the life cycle that begins just after fertilization of the female egg cell by the male sp ...

. A

mutation In biology, a mutation is an alteration in the nucleic acid sequence of the genome of an organism, virus, or extrachromosomal DNA. Viral genomes contain either DNA or RNA. Mutations result from errors during DNA or viral replication, ...

in a specific part of the FGFR2 gene alters the protein and causes prolonged signaling, which promotes the premature fusion of bones in the skull and feet,update 2011 this condition is inherited in an

autosomal dominant In genetics, dominance is the phenomenon of one variant (allele) of a gene on a chromosome masking or overriding the Phenotype, effect of a different variant of the same gene on Homologous chromosome, the other copy of the chromosome. The firs ...

pattern. Autosomal dominant means one copy of the altered gene in each cell is sufficient to cause the disorder.

Diagnosis

The diagnosis of Jackson–Weiss syndrome in an individual suspected of having the condition is done via the following: *

Genetic testing Genetic testing, also known as DNA testing, is used to identify changes in DNA sequence or chromosome structure. Genetic testing can also include measuring the results of genetic changes, such as RNA analysis as an output of gene expression, or ...

* Clinical presentation

Differential diagnosis

The DDx for this condition includes metopic synostosis, as well as Lambdoida synostosis.

Treatment

Treatment for Jackson–Weiss syndrome can be done through surgery for some facial features and feet. Secondary complications such as

hydrocephalus Hydrocephalus is a condition in which cerebrospinal fluid (CSF) builds up within the brain, which can cause pressure to increase in the skull. Symptoms may vary according to age. Headaches and double vision are common. Elderly adults with n ...

cognitive Cognition is the "mental action or process of acquiring knowledge and understanding through thought, experience, and the senses". It encompasses all aspects of intellectual functions and processes such as: perception, attention, thought, ...

impairment, can be averted via prompt surgery.

Epidemiology

In terms of epidemiology, Jackson–Weiss syndrome is a rare genetic disorder; the overall contribution of FGFR mutation to the condition is not clear.

References

External links

{{DEFAULTSORT:Jackson-Weiss syndrome Rare syndromes Autosomal dominant disorders Syndromes affecting the eye Cell surface receptor deficiencies Syndromes with craniofacial abnormalities